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When I lived in Ann Arbor, my children attended a public school where upwards of 15% of kids were not vaccinated for mumps because their left-wing parents didn’t trust the vaccine industry. Meanwhile on the right end of the political spectrum, Tea Party heart throb Michelle Bachman famously accused vaccines of causing autism. How is it that such an advanced technologic country harbors so many vaccine luddites?

A quick glance at the U.S. small pox epidemic of 1900 offers a clue.

At the turn of the 20th century, the United States had managed to avoid a major smallpox epidemic for the better part of a generation. Then a small wave of illness washed over communities of black farmers and laborers in a few southeastern states. The white community wasn’t alarmed however, believing the disease, which some called “nigger itch,” would stay contained to that population, who they were convinced had brought it upon themselves through one or another vice. As one local newspaper put it at the time: “Up to the present, no white people have been attacked and there is positively no occasion for alarm.”

Then of course the disease began spreading to white people. The smallpox virus, it turns out, was colorblind. Yet although white people did become alarmed at this point, they didn’t turn out in droves to get vaccines. Instead, a vocal minority argued vehemently that the vaccine was of no benefit.

It should have been obvious to even casual observers that the smallpox vaccine was a lifesaver. During the Franco-Prussian War of 1870-1871, you see, a smallpox epidemic had swept through Europe killing millions of citizens. The French army, which had half-heartedly vaccinated some of its troops, fared better than the population, but still saw over 23,000 troops fall victim to this terrible scourge. Meanwhile on the other side of the battle lines, the Prussian army, almost all of whom had been vaccinated, remained strong. Out of over 800,000 troops, only 457 died from smallpox.

Good policies often depend on good evidence. In healthcare, our gold standard for good evidence is the randomized controlled trial, in which, for example, half the patients receive a new drug and half receive a placebo. When the drug and placebo patients are determined at random, we can be pretty confident that any subsequent differences between the groups—like a higher mortality rate in the placebo group—occur because one group got the drug and the other didn’t.

But sometimes, non-experimental evidence is so striking that conducting a randomized trial—withholding the new intervention from half of an experimental population—feels immoral. That’s one reason there has never been a randomized trial of the smallpox vaccine. Indeed, it is why many early medical advances became standard of care without anyone seeing the need for a placebo controlled experiment.

Yet a mere thirty years after the end of the Franco-Prussian War, when the smallpox epidemic swept through the United States, a whole host of intelligent people refused to be vaccinated, convinced that the vaccine did more harm than good.

How could they hold this belief? For starters, the United States had much stronger libertarian leanings than places like France and Germany. But another fascinating phenomenon also contributed to people’s anti-vaccine views: people didn’t believe the evidence. They remained unconvinced because of what us in the medical research world would call concern about “confounding.”

A confound occurs in research when two groups differ not only in the intervention of interest, but also in some other possibly unmeasured way. This makes it hard to tell whether the difference between the groups is caused by the intervention in question--the vaccine in this case--or from this other factor.